Fatty liver disease is a globally widespread disease. The identification of valid biomarkers and targets for potential treatments requires in-depth knowledge about the pathophysiology of the postprandial liver. The study will consist of seven work packages (WP) including blood tests and liver biopsies taken after fasting or ingestion of a standardized meal in: healthy controls (WP 1), patients with NAFLD (WP 2), and patients with cirrhosis (WP 3) ; before and after a standardised meal in healthy controls (WP 4), and before and after glucagon in healthy controls (WP5), patients with NAFLD (WP6), and patients with T2DM and NAFLD (WP7).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
87
Standardised meal (Nutridrink, Nutricia, 300 kcal, 18.4 g carbohydrates, 5.8 g fat, 12 g protein).
Intravenous bolus of 0.2 mg glucagon
Gastrounit, Copenhagen University Hospital Hvidovre
Hvidovre, Capital Region Denmark, Denmark
Postprandial phosphoproteomic changes in liver tissue in healthy individuals
Phosphorproteomic changes will be performed using MS-based approach that allows identification of phosphorylations sites at proteins in the liver. The comparison will be done between 'fasted' and 'postprandial' samples in healthy individuals.
Time frame: 60 minutes after the meal administered at the study day
Postprandial phosphoproteomic changes in liver tissue between healthy participants and patients with cirrhosis or patients with NAFLD.
Phosphorproteomic changes will be performed using MS-based approach that allows identification of phosphorylations sites at proteins in the liver. The comparison will be done between 'fasted' and 'postprandial' samples in patients with cirrhosis and in patients with NAFLD and between healthy participants and patients with cirrhosis and patients with NAFLD.
Time frame: 60 minutes after the meal administered at the study day
Postprandial proteomic, metabolomic and transcriptomic changes in liver tissue in healthy individuals and compared to patients with cirrhosis and patients with NAFLD
Proteomic, metabolomic and transcriptomic changes will be performed using MS-based approaches and Next generation sequencing that allows identification of proteins, metabolites, RNA-transcripts in the liver. The comparison will be done between 'fasted' and 'postprandial' samples in healthy participants, patients with cirrhosis, and patients with NAFLD and between healthy participants and patients with cirrhosis and patients with NAFLD.
Time frame: 60 minutes after the meal administered at the study day
Postprandial proteomic, metabolomic and Peptidomic changes in blood obtained from liver vein and peripheral vein in healthy individuals and compared to patients with cirrhosis and patients with NAFLD
Proteomic, metabolomic and hormonal changes will be performed using MS-based approaches and ELISAs that allows identification and measurements of proteins, metabolites and hormones from the liver. The comparison will be done between 'fasted' and 'postprandial' samples in healthy individuals, patients with cirrhosis, and patients with NAFLD and between healthy participants and patients with cirrhosis and patients with NAFLD.
Time frame: 120 minutes after the meal administered at the study day
Postprandial phosphoproteomics, proteomic, metabolomic and transcriptomic changes in liver tissue in healthy individuals.
Phosphoproteomic, proteomic, metabolomic and transcriptomic changes will be performed using MS-based approaches and Next generation sequencing that allows identification of proteins, metabolites, RNA-transcripts in the liver. The comparison will be done between 'fasted' (before) and 'postprandial' (after) samples in healthy participants (paired).
Time frame: 30 minutes after the meal administered at the study day
Postprandial proteomic, metabolomic and Peptidomic changes in blood obtained from liver vein and peripheral vein in healthy individuals.
Proteomic, metabolomic and hormonal changes will be performed using MS-based approaches and ELISAs that allows identification and measurements of proteins, metabolites and hormones from the liver. The comparison will be done between 'fasted' (before) and 'postprandial' (after) samples in in healthy participants (paired).
Time frame: 120 minutes after the meal administered at the study day
Effect of exogenous glucagon on changes in liver phosphoproteomics, proteomics, metabolomics, and transcriptomics in healthy individuals and compared to patients with NAFLD and patients with T2DM and NAFLD.
Phosphoproteomic, proteomic, metabolomic and transcriptomic changes will be performed using MS-based approaches and Next generation sequencing that allows identification of proteins, metabolites, RNA-transcripts in the liver. The comparison will be done between 'fasted'/baseline samples and samples obtained after glucagon injection (paired) in healthy individuals, in patients with NAFLD, and in patients with T2DM and NAFLD and between healthy participants and patients with NAFLD and patients with T2DM and NAFLD.
Time frame: 30 minutes after the glucagon administered at the study day
Effect of exogenous glucagon on changes in phosphoproteomics, proteomics, metabolomics and peptidomic in blood obtained from liver vein and peripheral vein in healthy individuals and compared to patients with NAFLD and patients with T2DM and NAFLD
Proteomic, metabolomic and hormonal changes will be performed using MS-based approaches and ELISAs that allows identification and measurements of proteins, metabolites and hormones from the liver. The comparison will be done between 'fasted'/baseline samples and samples obtained after glucagon injection (paired) in healthy individuals, in patients with NAFLD, and in patients with T2DM and NAFLD and between healthy participants and patients with NAFLD and patients with T2DM and NAFLD.
Time frame: 120 minutes after the glucagon administered at the study day
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